Prevention of cardiac inefficiency in type 2 diabetes by means of high-intensity exercise training

Type 2 diabetes is associated with altered myocardial metabolism, reduced cardiac performance and reduced cardiac efficiency (cardiac work per unit oxygen consumption). The long-term objective of the present project is to understand the mechanisms behind diabetic cardiomyopathy, an example of cardiac contractile dysfunction. We hypothesize that reduced cardiac efficiency is a major factor contributing to cardiac dysfunction in the diabetic heart. The specific questions asked in this proposal is whether re duced cardiac efficiency in diabetes is related to (i) increased cost of E-C coupling because of diastolic Ca2+-leakage from the sarcoplasmic reticulum via ryanodine receptors and/or (ii) altered myocardial metabolism due to the high lipid load, resulting in mitochondrial dysfunction. The practical work related to the project will be carried out at the University of Tromsø (mouse heart perfusions, echocardiography) and NTNU (murine and human cardiomyocyte studies). Both institutions have excellent infras tructures for the proposed research with all the necessary state-of-the-art equipment (imaging facilities including ultrasound scanner dedicated for small animals, established pressure-volume technology, well equipped metabolic laboratory, mouse training facilities). This project will combine the expertise of the research groups of local project managers, Terje Larsen (cardiac function and metabolism) and Ulrik Wisløff (exercise training and heart failure). In addition, David Severson (Calgary/ adjunct Pr ofessor at UiT) will provide important input to the project by serving as a scientific consultant/advisor. The anticipated application potential of the project findings is to determine the role of cardiac inefficiency in the development of diabetic cardi omyopathy and to provide a scientific rationale for exercise being a sound and useful alternative to pharmacological treatment of the disease.